T cells develop in the thymus from hematopoietic progenitors. We have previously shown that normal migration of progenitors to the thymus uses two homing molecules, CCR7 and CCR9. However, we have now found that progenitor migration to the thymus after conditioning irradiation during bone marrow transplantation is independent of CCR7 and CCR9. Unexpectedly, we find that inhibition of other homing molecules can dramatically improve thymic reconstitution after bone marrow transplantation. We propose to identify and characterize progenitors homing both the normal thymus and after bone marrow transplantation, to identify and characterize the homing molecules that are used by progenitors for thymic homing after irradiation. Further, we will determine whether the ectopic expresion or inhibition of homing molecules will allow a broader range of blood progenitors to migrate to the thymus and improve T lymphopoiesis after bone marrow transplantation, and understand what the underlying mechanisms might be. ! PUBLIC HEALTH RELEVANCE: The identity of progenitors homing to the thymus, and the homing molecules used by cells to get to the thymus, is not well understood. In this proposal, we will identify the cells homing to the thymus normally and after bone marrow transplantation. We will identify and characterize the molecules that are for thymic homing, and determine whether the ectopic expression of homing molecules will allow a broader range of blood progenitors to migrate to the thymus and improve T lymphopoiesis after bone marrow transplantation.